Department of Immunology,; Department of Otorhinolaryngology, Head and Neck Surgery.
Department of Immunology.
Allergol Int. 2010 Sep;59(3):313-319. doi: 10.2332/allergolint.10-SC-0172. Epub 2010 May 25.
Transforming growth factor-beta (TGF-beta) levels are elevated in the nasal mucosa in allergic rhinitis. However, because TGF-beta is secreted extracellulary in latent complexes, it remains unclear whether the local TGF-beta expression actually drives active signaling and affects the pathophysiology of allergic rhinitis. The objective of this study is to investigate whether TGF-beta signaling is activated in allergic rhinitis and plays a role in the pathophysiology of allergic rhinitis.
An ovabumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis was established and phosphorylation of Smad2 in the nasal mucosa was examined by immunohistochemistry. In addition, the effects of the pharmacological inhibition of endogenous TGF-beta signaling on the allergic rhinitis model were histologically examined. Furthermore, phosphorylation of Smad2 in the nasal mucosa samples obtained from patients with allergic rhinitis was also evaluated.
In the mouse model of allergic rhinitis, OVA challenge induced phosphorylation of Smad2 predominantly in epithelial cells in the nasal mucosa. In addition, the administration of an inhibitor of TGF-beta type I receptor kinase activity during OVA challenge suppressed goblet cell hyperplasia in the nasal mucosa. Furthermore, phosphorylated Smad2 expression increased in nasal epithelial cells in patients with allergic rhinitis.
These results suggest that TGF-beta signaling is activated in epithelial cells in the nasal mucosa in allergic rhinitis and may contribute to the development of goblet cell hyperplasia.
变应性鼻炎患者的鼻黏膜中转化生长因子-β（TGF-β）水平升高。然而，由于 TGF-β 以潜伏复合物的形式分泌到细胞外，因此尚不清楚局部 TGF-β表达是否实际上驱动了活性信号转导，并影响了变应性鼻炎的病理生理学。本研究的目的是探讨 TGF-β信号转导是否在变应性鼻炎中被激活，并在变应性鼻炎的病理生理学中发挥作用。
建立卵清蛋白（OVA）致敏和鼻内攻击的变应性鼻炎小鼠模型，并通过免疫组织化学检查鼻黏膜中 Smad2 的磷酸化。此外，还通过组织学检查内源性 TGF-β信号转导的药理学抑制对变应性鼻炎模型的影响。此外，还评估了从变应性鼻炎患者的鼻黏膜样本中 Smad2 的磷酸化。
在变应性鼻炎小鼠模型中，OVA 攻击主要诱导鼻黏膜上皮细胞中 Smad2 的磷酸化。此外，在 OVA 攻击期间给予 TGF-β Ⅰ型受体激酶活性抑制剂可抑制鼻黏膜中的杯状细胞增生。此外，变应性鼻炎患者的鼻上皮细胞中磷酸化 Smad2 的表达增加。
这些结果表明，TGF-β信号转导在变应性鼻炎的鼻黏膜上皮细胞中被激活，可能有助于杯状细胞增生的发展。
